HMG-CoA reductase has been shown to be the major regulatory enzyme in hepatic cholesterol biosynthesis. In view of the probable relationship between elevated levels of plasma cholesterol and atherosclerosis, an understanding of the regulation of cholesterol biosynthesis by this enzyme is of medical importance. We have devised techniques for the purification of this enzyme, and titrations of HMG-CoA reductase at various stages of purification with HMG-CoA reductase antiserum show that the enzyme can exist in more active and less active forms.